1. Field of the Invention
This invention relates to analysis of molecular samples.
More particularly, the present invention relates to manipulation of molecules through the use of electric fields.
2. Prior Art
Identification of molecular structure has become very important in many industries. In particular, biological molecules such as nucleic acids and proteins are analyzed to form the basis of clinical diagnostic assays. The procedures utilized often involved large numbers of repetitive steps which consume large amounts of time. With the advent of large projects such as the human genome project, faster and less complex techniques were required.
Simpler and quicker analysis of molecules has been provided by the development of devices including a monolithic array of test sites formed on a substrate. Each site includes probes therein to bond with predetermined target molecules from samples applied to the device. The binding of a molecule to a probe is noted, and that molecule is identified. There are many techniques for determining which test sites have molecules bonded to them including autoradiography, optical detection and electronic detection. The use of monolithic devices with an array of test sites provides a procedure which permits the testing of a great many samples quickly. However, there are numerous problems with the use of these devices which increase complexity and decrease accuracy.
For example, nucleic acid hybridization analysis is a procedure wherein target DNA or RNA strands bond to probes which are typically oligonucleotide sequences. The analysis generally involves detecting very small numbers of a specific target nucleic acid sequence among a large number of non-target sequences. Thus, the concentration of target molecules proximating the appropriate test site is unfavorable. Furthermore, when a sample is composed of a large number of sequences, partial hybridization of similar sequences can occur. These problems lead to a loss in sensitivity and accuracy during analysis.
These problems have generally been overcome by free field electrophoresis and the use of addressable matrices. Molecules in a sample can be transported by free field electrophoresis to any specific test site where the molecules are concentrated. The sensitivity for detecting a specific molecular structure is enhanced because of the increase in concentration of molecules available for binding to the site. Any unbound molecules can be removed by reversing the polarity at the site. Furthermore, in nucleic acid hybridizations, partial hybridizations, which form a much weaker bond than the full hybridization, can be severed by the reverse polarization at specific sites. Thus, accuracy and sensitivity are greatly increased.
The problem is that for each test site of the matrix to be addressable, electrodes and leads must be provided for each test site. As device size shrinks and the number of test sites increases, the complexity and expense of forming devices with a plurality of isolated electrodes and associated leads also increases. While large numbers of electrodes and micro-electrodes can be easily formed, addressably contacting each with the use of leads becomes increasingly complex and expensive as the number of electrodes increases.
It would be highly advantageous, therefore, to remedy the foregoing and other deficiencies inherent in the prior art.
Accordingly, it is an object of the present invention to provide a new and improved method and apparatus for manipulating molecules.
Another object of the present invention is to provide a method and apparatus for manipulating molecules using wireless contacts for a spatially addressable array of electrodes.
And another object of the present invention is to provide a method and apparatus for analyzing molecules which is fast and efficient.
Still another object of the present invention is to provide a method and apparatus which can include large probe arrays.
Yet another object of the present invention is to provide a method and apparatus which can selectively apply a positive or negative potential or combinations of both.